BackgroundVisual loss in glaucoma is associated with pathological changes in retinal ganglion cell (RGC) axons and a slow decline in the RGC population. Age and elevated intraocular pressure (IOP) are the main risk factors for glaucomatous loss of vision. Several studies have implicated the proinflammatory cytokine tumor necrosis factor- α (TNF-α) as a link between elevated IOP and RGC death, but the cellular source of TNF-α and its causative role in RGC death remain uncertain. Here, using a rat model of glaucoma, we investigated the source of elevated TNF- α and examined whether Etanercept, a TNF-α blocker that is in common clinical use for other indications, is protective against RGC death.Methodology/Principal FindingsEpiscleral vein cauterization (EVC) caused intraocular pressure (IOP) to be elevated for at least 28 days. IOP elevation resulted in a dramatic increase in TNF-α levels within a few days, axonal degeneration, and a 38% loss of RGCs by 4 weeks. Immunostaining coupled with confocal microscopy showed that OHT induced robust induction of TNF-α in Iba-1-positive microglia around the optic nerve head (ONH). Despite persistent elevation of IOP, Etanercept reduced microglial activation, TNF-α levels, axon degeneration in the optic nerve, and the loss of RGCs.Conclusions/SignificanceOcular hypertension (OHT) triggers an inflammatory response characterized by the appearance of activated microglia around the ONH that express TNF-α. Blocking TNF-α activity with a clinically approved agent inhibits this microglial response and prevents axonal degeneration and loss of RGCs. These findings suggest a new treatment strategy for glaucoma using TNF- α antagonists or suppressors of inflammation.
Autocrine VEGF-A enhanced RPE cell survival under oxidative stress; the autocrine VEGF-A/VEGF-R2/PI3K/Akt pathway is involved. Neutralization of VEGF-A signaling, as in eyes with age-related macular degeneration, may influence RPE cell survival.
Mean subfoveal choroidal thickness in the acute phase of Behcet's uveitis was significantly greater than that in the quiescent phase (398.77 ± 155.59 μm versus 356.72 ± 141.09 μm; P = 0.004). Subfoveal choroidal thickness in the quiescent phase was also significantly greater than that of the healthy population (259.96 ± 65.16 μm; P < 0.0001). There was a statistically significant association between the change in subfoveal choroidal thickness and the change in vascular leakage revealed by FA (ρ = 0.381, P = 0.046). Subfoveal choroidal thickness in the uninvolved fellow eyes of patients with unilateral Behcet's uveitis was also evaluated and it was significantly greater than that of the healthy population (n = 13 eyes; P = 0.001) CONCLUSIONS: This study found choroidal thickening during the active phase of Behcet's posterior uveitis. Subfoveal choroidal thickness during the quiescent phase was also significantly greater than in normal eyes. The degree of reduction in choroidal thickening was significantly correlated with improvement in retinal vascular leakage as revealed by FA.
The incidence of PCV in Korean exudative AMD patients was relatively high compared with that in other ethnic groups. As in other Asian patient populations, PCV occurred more commonly in men and was predominantly unilateral.
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